Micro-dosing pumps and valves

ABSTRACT

A fluid mircro pump or valve of a two-stage pulsatile peristaltic type. The pump body has an inlet port and an outlet port. First and second layers of SiO are formed on an Si wafers disposed in face-to-face relationship within the body. The first layers define flexible diaphragms bulge, responsive to a first fluid pressure, between a flat shape and a dome shape containing a pumping chamber. The domes overlap laterally so that fluid is pumped from on chamber to the other as the diaphragms are bulged in serial fashion. Control chambers apply fluid pressure to bulge the domes.

CROSS-REFERENCE TO PRIOR APPLICATION

[0001] This application claims the benefit under 35 USC §119(e) of U.S. provisional application serial No. 60/362,972 filed Mar. 7, 2002.

BACKGROUND OF THE INVENTION

[0002] 1.0 Field of the Invention

[0003] This invention relates in general to microelectromechanical systems (MEMS) pumps and valves, and more particularly to systems capable of micro-dosing small aliquots of aqueous solutions for use in fields such as genomics and proteomics.

[0004] 2.0 Description of the Related Art

[0005] The Human Genome Project and the Department of Health and Human Services Protein Structural Initiative have stimulated rapid growth in genomics and proteomics research. High-throughput systems for drug discovery and DNA analysis employ channels to increase the number of experiments done simultaneously. There is a growing need for dispensing systems capable of micro-dosing small aliquots of aqueous solutions. Sample size must become smaller because DNA is expensive. Thus internal dead volume of the entire system becomes critical because in a large volume, a small sample size is lost. Further, samples must be of uniform volume, the wetted surfaces are restricted to specific materials, and temperatures and electrical potentials are limited.

[0006] In a wide variety of genomics and proteomics analysis systems it is necessary convey nanoliter and picoliter samples from the supply reservoir to the test apparatus. In some systems, samples are transferred from the reservoir to a flat surface by means of capillary tubes that are used to “print” on a flat surface. In others, the fluid is ejected from nozzles into reaction chambers. In both cases, a method of micro-dosing is required that can move fluid volumes of sample from reservoir to reaction site in a repeatable manner. Conventional valves, based on solenoid actuation, besides being large compared to the samples to be transferred, are difficult to “tune” so that uniform samples can be transferred: sample sizes vary randomly from nozzle to nozzle and from pulse to pulse within the same nozzle. Assembly of more than a few channels, using discrete components, becomes prohibitively labor intensive and expensive. Newer methods, such as microfabrication techniques, are increasingly seen as cost effective technologies for development and manufacture of integrated Microsystems.

[0007] System design is in now transition. Conventional systems use robots to load wells in genomics and proteomics analysis. This is wasteful: a significant part of each load must remain in the well. Eventually all processes will be integrated into a chip. But even then there will be a need to transfer small quantities, under computer control, from place to place. Thus the pump/valve system described herein is needed for present robotics oriented systems but will be just as critical to integrated systems.

OBJECTS

[0008] It is a general object of the invention to provide a new and improved fluid valve/pump system for use in microelectromechanical systems.

[0009] It is a further object to provide fluid valve/pump systems capable of micro-dosing small aliquots of aqueous solutions for use in fields such as genomics and proteomics.

BRIEF DESCRIPTION OF THE DRAWINGS

[0010]FIG. 1 is a side elevational view of a fluid mircro pump in accordance with one preferred embodiment of the invention.

[0011]FIG. 2 is a side elevational view taken along the line 2-2 of FIG. 1.

[0012]FIG. 3 is a schematic cross sectional view of a unit cell in a pump array showing one condition of the two diaphragms in the pump of FIG. 1.

[0013]FIG. 4 is a schematic cross sectional view of a unit cell in a pump array showing another condition of the two diaphragms in the pump of FIG. 1.

[0014]FIG. 5 is a schematic cross sectional view of a unit cell in a pump array showing another condition of the two diaphragms in the pump of FIG. 1.

[0015]FIG. 6 is a schematic cross sectional view of a unit cell in a pump array showing another condition of the two diaphragms in the pump of FIG. 1.

[0016]FIG. 7 is a schematic side view of a linear array of four of the pumps of FIG. 1.

[0017]FIG. 8 is a schematic cross section of one of the diaphragms in the pump of FIG. 1.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] In the drawings, FIGS. 1 6 illustrate generally at 10 a fluid mircro pump which is shown within a micro-tier well 12 which contains a sample fluid which is to be pumped. Pump 10 is of a two-stage pulsatile peristaltic type. A microprocessor controller is suitable for use in cycling the pumps.

[0019] Fluid intake is via a port 14 at the lower end below the fluid surface 15. An outlet 16 at the upper end of the pump leads to an accumulator, not shown. Control pressure ports 18 and 20 are also at the upper end.

[0020] A plurality of the pumps 10 can be arrayed together in the manner described in connection with FIG. 4. Each pump is comprised of two chambers, a first chamber 22 (FIG. 4) and a second chamber 24 (FIG. 5). In the first phase of a pumping cycle, the first chamber is filled from its reservoir through an intake port 26. In the second phase of the cycle, the contents of the first chamber are transferred to the second chamber 24. The second chamber is then emptied into a capillary tube through an outlet port 27. The dashed lines 23 and 25 shown vias formed in the wafers for communication fluid between the ports and chambers.

[0021] The chambers 22 and 24 are formed in the surfaces of two solid silicon (Si) wafers 21 and 23 using known microfabrication techniques to etch thin diaphragms 30 and 32. The facing sides of the wafers are oxidized, by exposure to H₂O while heated, to form a layer of SiO. Because the SiO layer occupies a greater volume than the Si from which it is formed, the internal stresses that are created cause the the SiO layer to buckle down into the dome shaped diaphragms. The diaphragms are approximately 1 mm in diameter and the domes are a few microns high. Each such dome has a volume of about 25 picoliters. The domes formed by the diaphragms are flexible and will change shape if pressure is applied. In an array of the pumps, when the appropriate amount of pneumatic pressure is applied to the front surface of the wafer then all of the diaphragms will buckle toward the opposite side. Similarly, pneumatic pressure applied to the reverse side of the wafer will cause the volume inside the dome to diminish. This is the origin of the pumping action.

[0022] For each pump, the two wafers 21 and 23 are bonded face-to-face, positioned to form pairs of chambers that partially overlap. When the first chamber of each pair is changed from flat shape to dome shape, fluid is drawn into it. When the first chamber is flattened while the second is domed, its contents are transferred to the other member of the pair. If both diaphragms of a pair are flattened in sequence, the contents are forced out through the outlet ports into a capillary tube (not shown). Cycling is accomplished by sequentially changing pressures on opposing sides of the wafer sandwich.

[0023] The dome shape is controlled by modulating fluid pressure in a control chamber 34 for diaphragm 32 and in a control chamber 36 for diaphragm 30.

[0024] The silicon/silicon oxide diaphragms change between two shapes—either domed or flattened. The volumes below the diaphragms comprise the control chambers that are sequentially pressurized and de-pressurized to force the diaphragms to flatten or bend. As the diaphragms change shape, the volumes change. Fluid is transported from the intake port, through the intake via, into the first chamber, then into the second chamber, then the output via and out through outlet port 27.

[0025] FIGS. 3-6 show four different stages for the two diaphragms. In the first stage of FIG. 3, both diaphragms are in closed position so that the volume they enclose is minimum. In transition to the second stage of FIG. 4, pressure on the lower diaphragm is decreased so that it forms a downwardly convex dome shape, causing pressure in chamber 22 to decrease which draws fluid in through the intake port.

[0026] In transition to the third stage of FIG. 5, the upper diaphragm is opened while simultaneously closing the lower diaphragm so that the quantity of fluid is transferred from chamber 22 to chamber 24. The cycle is completed by increasing pressure in control chamber 34 above diaphragm 32 so the fluid is forced through the outlet port. Completion of this stage returns the pump to the first stage in preparation for another cycle.

[0027]FIG. 6 shows the pump with both diaphragms un-pressurized so that there is a clear flow path through the two diaphragms and the inlet and outlet channels. This stage may be used of flushing the system between uses.

[0028]FIG. 7 shows any array of four identical pumps 42, 44, 46 and 48. Each array is shown in four possible states from states 50, 52, 54, and 56. Pumping is accomplished by iteratively repeating stages 52, 54 and 56. In state 50 the diaphragms are open for flushing. State 52 is the intake phase for each pump. State 54 transfer the contents of first chamber 58 to second chamber 60 in each pump. State 56 transfers the contents of chamber 60 through the outlet port of each pump into capillaries.

[0029] The volume enclosed by the curved membrane which forms the diaphragms can be approximately calculated if the curvature is assumed to be spherical. FIG. 8 show a cross section of a typical diaphragm of the invention having a wall thickness t, length L and height h. The radius of curvature is approximately L²8h. This radius is to be limited so that the strain in the surface of the membrane is about 0.5%.

[0030] Strain=0.005=t/R=8th/L²

[0031] Then if L is one millimeter and t is 10 microns, h=50 microns, and the volume enclosed is about 25×10⁶ microns³ or 25 picoliters.

[0032] Therefore one cycle of each pump can deliver about 25 picoliters of DNA-containing aqueous solution. Uniformity from one pump to another and from one cycle to another is extremely close. All pumps in an array operate in unison. Each pump can supply a fixed-volume aliquot of solution to a print head through a capillary tube or through a nozzle into a reaction site.

[0033] The pump system is capable of being flushed for cleaning and re-use. This may involve exposure to strongly basic solutions. The solutions contain NaOH at a pH of approximately 12. All materials wetted by fluids in the pumps must be compatible with biological basic fluids and basic chemistry. Acceptable material include glass (silicon dioxide), PEEK plastic, polystyrene, stainless steel and polypropylene plastic.

[0034] Since DNA links have two dangling negative charges, it is imperative that all material with which the liquid comes in contact have no net positive charge or the molecules will adhere to the surface and not easily be moved.

[0035] The system of dome shaped diaphragms in face-to-face relationship as described can also be applied as a valve for control of fluids. 

1. A device for micro-dose pumping or valving of a fluid, the device comprising a pump body having an inlet port and an outlet port, first and second layers disposed in face-to-face relationship within the body, the first layer being formed with a first diaphragm having an outer side, the diaphragm being sufficiently flexible to bulge, responsive to a first fluid pressure on a first outer side, between a flat shape and a first dome shape which projects away from the second layer and forms a first pumping chamber therewith, the second layer being formed with a second diaphragm having a second outer side, the second diaphragm being sufficiently flexible to bulge, responsive to a second fluid pressure on the second outer side, between a flat shape and a second dome shape which projects away from the first layer forms a second pumping chamber therewith, the first diaphragm being offset laterally with respect to the second diaphragm sufficient so that the first and second domes partially overlap to enable fluid transfer between the domes, and a flow channel in the body for communicating fluid from the inlet port to the first and second pumping chambers and the outlet port.
 2. A device as in claim 1 which further comprises control means for producing the first and second fluid pressure.
 3. A device as in claim 2 in which the control means comprises a first control chamber for containing the first pressure and a second control chamber for containing the second pressure, the first and second control chambers being in fluid communication with respective first and second outer sides.
 4. A device as in claim 1 having a plurality of the pump bodies, the first and second layers with the diaphragm in an array.
 5. A method for fabricating a micro-dose pump or valve comprising the steps of forming first and second flexible diaphragms of SiO on surfaces of respective first and second Si wafers, placing the surfaces in face-to-face relationship along a plane with the diaphragms in lateral overlapping relationship, enabling the first and second diaphragms to bulge from flat shapes toward respective first and second dome shapes in directions away from the plane with the domes enclosing respective first and second volumes and with the volumes being in fluid communication when the diaphragms are both bulged into the domes, causing a sample of fluid to enter the first volume when the first diaphragm is in the first dome shape, causing the sample to enter the second volume when the diaphragms are both bulged into the domes, and directing the sample to egress from the second volume when the second the diaphragm is in its flat shape.
 9. A device made by the method of claim
 8. 